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1.  Overall and worst gleason scores are equally good predictors of prostate cancer progression 
BMC Urology  2011;11:21.
Gleason scoring has experienced several modifications during the past decade. So far, only one study has compared the prognostic abilities of worst (WGS) and overall (OGS) modified Gleason scores after the ISUP 2005 conference. Prostatic needle biopsies are individually paraffin-embedded in 57% of European pathology laboratories, whereas the rest of laboratories embed multiple (2 - 6) biopsies per one paraffin-block. Differences in the processing method can have a far-reaching effect, because reporting of the Gleason score (GS) is different for individually embedded and pooled biopsies, and GS is one of the most important factors when selecting treatment for patients.
The study material consisted of needle biopsies from 236 prostate cancer patients that were endocrine-treated in 1999-2003. Biopsies from left side and right side were embedded separately. Haematoxylin-eosin-stained slides were scanned and analyzed on web-based virtual microscopy. Worst and overall Gleason scores were assessed according to the modified Gleason score schema after analyzing each biopsy separately. The compound Gleason scores (CGS) were obtained from the original pathology reports. Two different grade groupings were used: GS 6 or less vs. 7 vs. 8 or above; and GS 7(3 + 4) or less vs. 7(4 + 3) and 8 vs. 9-10. The prognostic ability of the three scoring methods to predict biochemical progression was compared with Kaplan-Meier survival analysis and univariate and multivariate Cox regression analyses.
The median follow-up time of the patients was 64.5 months (range 0-118). The modified GS criteria led to upgrading of the Gleason sums compared to the original CGS from the pathology reports 1999-2003 (mean 7.0 for CGS, 7.5 for OGS, 7.6 for WGS). In 43 cases WGS was > OGS. In a univariate analysis the relative risks were 2.1 (95%-confidence interval 1.8-2.4) for CGS, 2.5 (2.1-2.8) for OGS, and 2.6 (2.2-2.9) for WGS. In a multivariate analysis, OGS was the only independent prognostic factor.
All of the three Gleason scoring methods are strong predictors of biochemical recurrence. The use of modified Gleason scoring leads to upgrading of GS, but also improves the prognostic value of the scoring. No significant prognostic differences between OGS and WGS could be shown, which may relate to the apparent narrowing of the GS scale from 2-10 to 5-10 due to the recent modifications.
PMCID: PMC3193164  PMID: 21978318
2.  Stromal Activation Associated with Development of Prostate Cancer in Prostate-Targeted Fibroblast Growth Factor 8b Transgenic Mice12 
Neoplasia (New York, N.Y.)  2010;12(11):915-927.
Expression of fibroblast growth factor 8 (FGF-8) is commonly increased in prostate cancer. Experimental studies have provided evidence that it plays a role in prostate tumorigenesis and tumor progression. To study how increased FGF-8 affects the prostate, we generated and analyzed transgenic (TG) mice expressing FGF-8b under the probasin promoter that targets expression to prostate epithelium. Prostates of the TG mice showed an increased size and changes in stromal and epithelialmorphology progressing fromatypia and prostatic intraepithelial neoplasia (mouse PIN, mPIN) lesions to tumors with highly variable phenotype bearing features of adenocarcinoma, carcinosarcoma, and sarcoma. The development of mPIN lesions was preceded by formation of activated stroma containing increased proportion of fibroblastic cells, rich vasculature, and inflammation. The association between advancing stromal and epithelial alterations was statistically significant. Microarray analysis and validation with quantitative polymerase chain reaction revealed that expression of osteopontin and connective tissue growth factor was markedly upregulated in TG mouse prostates compared with wild type prostates. Androgen receptor staining was decreased in transformed epithelium and in hypercellular stroma but strongly increased in the sarcoma-like lesions. In conclusion, our data demonstrate that disruption of FGF signaling pathways by increased epithelial production of FGF-8b leads to strongly activated and atypical stroma, which precedes development of mPIN lesions and prostate cancer with mixed features of adenocarcinoma and sarcoma in the prostates of TG mice. The results suggest that increased FGF-8 in human prostate may also contribute to prostate tumorigenesis by stromal activation.
PMCID: PMC2978914  PMID: 21076617

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